The Children's Mercy variant characterization pipeline (RUNES: Rapid Understanding of Nucleotide variant Effect Software) is a multi-stage analysis pipeline for annotating and classifying human nucleotide variation detected through short read alignment. The long-term plan for the pipeline is to continually add characterizations and variant types as new tools/capabilities appear.
Variant characterizations are viewable and queryable through a lightweight web application. Characterization is divided into multiple independent stages that each record zero or more annotations for each variant according to the type of characterization being performed by the stage.
At the end of characterization, variant annotations are aggregated and submitted to a variant classifier which assigns an American College of Medical Genetics (ACMG) category to each based on the accumulated annotation evidence, with the most damaging category achieved being the final categorization.
Characterization stages use a variety of software and data from both internal and external sources. The stages include:
- ENSEMBL Variant Effect Predictor (VEP)
- Comparison with dbSNP
- CMH splice impact evaluator
- CMH transcript context characterizer
- Comparison with Human Gene Mutation Database (HGMD/GenomeTrax)